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Das Marfan-Syndrom und verwandte monogene Krankheiten der Aorta

Marfan syndrome and related monogenic diseases of the aorta

Zusammenfassung

Das Marfan-Syndrom (MFS) ist eine autosomal-dominant vererbte, pleiotrope Erkrankung des Bindegewebes mit einer Prävalenz von etwa 1:5000 Personen. Zwischen und auch innerhalb von Familien weisen betroffene Personen variable Kombinationen von Manifestationen im Herz-Kreislauf-System, Auge, Skelett sowie in der Lunge, Haut und Dura mater auf. Beim klassischen MFS treten viele Manifestationen während oder kurz vor der Pubertät auf; schwerwiegende Komplikationen sind vor dem Erwachsenenalter eher selten.

Viele Patienten imponieren durch einen sog. marfanoiden Körperhabitus mit Hochwuchs, langen und schmalen Gliedmaßen (Dolichostenomelie), einer langen und schmalen Kopfform (Dolichozephalie) und anderen skelettalen Auffälligkeiten wie Pes planus oder Skoliose. Eine Skoliose tritt bei etwa 60% der Betroffenen auf, Pectus excavatum oder carinatum bei etwa zwei Dritteln. Eine fast immer beidseitige Ectopia lentis kommt bei vielen Patienten vor (etwa 60%).

Bei manchen Patienten bestehen therapiepflichtige Komplikationen wie schwerwiegende Skoliose oder Trichterbrust, Spontanpneumothorax, Netzhautablösung oder ein durch Linsenluxation hervorgerufenes akutes Glaukom. Die gefährlichste Komplikation ist jedoch die akute Dissektion der aufsteigenden Aorta, die in aller Regel die Folge einer langsam fortschreitenden Aortendilatation darstellt. Vor der Einführung moderner Therapieformen, die in diesem Artikel behandelt werden, betrug die durchschnittliche Lebenserwartung MFS-Betroffener nur 32 Jahre. Heute kann bei Betreuung in multidisziplinären Zentren von einer durchschnittlichen Lebenserwartung von über 60 Jahren ausgegangen werden. Dieser Artikel bietet dem Leser einen Überblick über bewährte und neue Diagnose- und Therapiekonzepte für MFS und andere hereditäre Erkrankungen der Aorta.

Abstract

Marfan syndrome (MFS) is an autosomal dominant, pleiotropic disease of the connective tissue with a prevalence of about 1 in 5000 persons. MFS is characterized by manifestations in the cardiovascular system, eye, skeleton, lung, skin, and dura mater that show a high degree of intra- and interfamilial variability. Many manifestations develop during or shortly before puberty; severe complications rarely occur before adulthood.

Many patients with MFS display a so-called marfanoid habitus with tall stature, dolichostenomelia (long, narrow extremities), dolichocephaly (disproportionately long and narrow head), as well as other skeletal abnormalities such as scoliosis and pes planus. Scoliosis occurs in approximately 60% of those affected, pectus deformities in up to two thirds. Ectopia lentis is seen in many patients with MFS and is almost always bilateral.

MFS is characterized by a high risk for complications such as severe scoliosis or pectus deformities, spontaneous pneumothorax, retinal detachment, or glaucoma secondary to lens luxation. The most severe complications occur in the cardiovascular system, including in particular acute dissection of the ascending aorta, which generally follows a long period of progressive aortic dilatation. Before the introduction of modern treatment modalities, the average life expectancy of persons with MFS was estimated to be 32 years. Today, with medical care in multidisciplinary centers, an average life expectancy of over 60 years can be achieved. This article offers a review of established and novel concepts for the diagnosis and treatment of MFS and other hereditary diseases of the aorta.

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Literatur

  1. 1.

    Arslan-Kirchner M, von Kodolitsch Y, Schmidtke J (2008) The importance of genetic testing in the clinical management of patients with Marfan syndrome and related disorders. Dtsch Arztebl Int 105:483–491

    PubMed  Google Scholar 

  2. 2.

    Baetens M, Van Laer L, De Leeneer K et al. (2011) Applying massive parallel sequencing to molecular diagnosis of Marfan and Loeys-Dietz syndromes. Hum Mutat: 2011 May 3 [Epub ahead of print]. doi: 10.1002/humu.21525.

    Google Scholar 

  3. 3.

    Couzin-Frankel J (2011) Frightening risk of Marfan syndrome, and potential treatment, elucidated. Science 332:297

    PubMed  Article  CAS  Google Scholar 

  4. 4.

    Faivre L, Collod-Beroud G, Loeys BL et al. (2007) Effect of mutation type and location on clinical outcome in 1,013 probands with Marfan syndrome or related phenotypes and FBN1 mutations: an international study. Am J Hum Genet 81:454–466

    PubMed  Article  CAS  Google Scholar 

  5. 5.

    Guo DC, Papke CL, Tran-Fadulu V et al. (2009) Mutations in smooth muscle alpha-actin (ACTA2) cause coronary artery disease, stroke, and moyamoya disease, along with thoracic aortic disease. Am J Hum Genet 84:617–627

    PubMed  Article  CAS  Google Scholar 

  6. 6.

    Habashi JP, Judge DP, Holm TM et al. (2006) Losartan, an AT1 antagonist, prevents aortic aneurysm in a mouse model of Marfan syndrome. Science 312:117–121

    PubMed  Article  CAS  Google Scholar 

  7. 7.

    Loeys BL, Dietz HC, Braverman AC et al. (2010) The revised Ghent nosology for the Marfan syndrome. J Med Genet 47:476–485

    PubMed  Article  CAS  Google Scholar 

  8. 8.

    Loeys BL, Schwarze U, Holm T et al. (2006) Aneurysm syndromes caused by mutations in the TGF-beta receptor. N Engl J Med 355:788–798

    PubMed  Article  CAS  Google Scholar 

  9. 9.

    Mortensen K, Aydin MA, Rybczynski M et al. (2009) Augmentation index relates to progression of aortic disease in adults with Marfan syndrome. Am J Hypertens 22:971–979

    PubMed  Article  Google Scholar 

  10. 10.

    Pannu H, Tran Fadulu V, Chang J et al. (2005) Mutations in transforming growth factor-beta receptor type II cause familial thoracic aortic aneurysms and dissections. Circulation 112:513–520

    PubMed  Article  CAS  Google Scholar 

  11. 11.

    Pepin M, Schwarze U, Superti-Furga A, Byers PH (2000) Clinical and genetic features of Ehlers-Danlos syndrome type IV, the vascular type. N Engl J Med 342:673–680

    PubMed  Article  CAS  Google Scholar 

  12. 12.

    Robinson PN, Arteaga-Solis E, Baldock C et al. (2006) The molecular genetics of Marfan syndrome and related disorders. J Med Genet 43:769–787

    PubMed  Article  CAS  Google Scholar 

  13. 13.

    Robinson PN, Neumann LM, Demuth S et al. (2005) Shprintzen-Goldberg syndrome: fourteen new patients and a clinical analysis. Am J Med Genet A 135:251–262

    PubMed  Google Scholar 

  14. 14.

    Rybczynski M, Bernhardt AMJ, Rehder U et al. (2008) The spectrum of syndromes and manifestations in individuals screened for suspected Marfan syndrome. Am J Med Genet A 146A:3157–3166

    PubMed  Article  Google Scholar 

  15. 15.

    Rybczynski M, Koschyk D, Karmeier A et al. (2010) Frequency of sleep apnea in adults with the Marfan syndrome. Am J Cardiol 105:1836–1841

    PubMed  Article  Google Scholar 

  16. 16.

    Rybczynski M, Koschyk DH, Aydin MA et al. (2007) Tissue doppler imaging identifies myocardial dysfunction in adults with Marfan syndrome. Clin Cardiol 30:19–24

    PubMed  Article  Google Scholar 

  17. 17.

    Rybczynski M, Treede H, Sheikhzadeh S et al. (2011) Predictors of outcome of mitral valve prolapse in patients with the Marfan syndrome. Am J Cardiol 107:268–274

    PubMed  Article  Google Scholar 

  18. 18.

    Shores J, Berger KR, Murphy EA, Pyeritz RE (1994) Progression of aortic dilatation and the benefit of long-term beta-adrenergic blockade in Marfan’s syndrome. N Engl J Med 330:1335–1341

    PubMed  Article  CAS  Google Scholar 

  19. 19.

    Singh KK, Rommel K, Mishra A et al. (2006) TGFBR1 and TGFBR2 mutations in patients with features of Marfan syndrome and Loeys-Dietz syndrome. Hum Mutat 27:770–777

    PubMed  Article  CAS  Google Scholar 

  20. 20.

    Kodolitsch Y von, Robinson PN (2007) Marfan syndrome: an update of genetics, medical and surgical management. Heart 93:755–760

    Article  Google Scholar 

  21. 21.

    Yap S (2003) Classical homocystinuria: vascular risk and its prevention. J Inherit Metab Dis 26:259–265

    PubMed  Article  CAS  Google Scholar 

  22. 22.

    Yetman AT, Bornemeier RA, McCrindle BW (2003) Long-term outcome in patients with Marfan syndrome: is aortic dissection the only cause of sudden death? J Am Coll Cardiol 41:329–332

    PubMed  Article  Google Scholar 

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Danksagung

Forschungsförderung: European Commission (FAD; HEALTH-F2-2008-200647)

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Der korrespondierende Autor gibt an, dass kein Interessenkonflikt besteht.

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Correspondence to P.N. Robinson or Y. von Kodolitsch.

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Robinson, P., Arslan-Kirchner, M., Gehle, P. et al. Das Marfan-Syndrom und verwandte monogene Krankheiten der Aorta. medgen 23, 407–420 (2011). https://doi.org/10.1007/s11825-011-0285-9

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Schlüsselwörter

  • Marfan-Syndrom
  • Fibrillin-1
  • Aortendissektion
  • Loeys-Dietz-Syndrom
  • Aortenaneurysma

Keywords

  • Marfan syndrome
  • Fibrillin-1
  • Aneurysm, dissecting
  • Loeys-Dietz syndrome
  • Aortic aneurysm